Method for combating marek&#39;s disease in poultry

ABSTRACT

A METHOD OF PREVENTING OR TREATING MAREK&#39;&#39;S DISEASE IN POULTRY BY ADMINISTERING PHOSPHONOACETIC ACID OR ITS SALTS.

United States Patent 3,836,650 METHOD FOR COMBATING MAREKS DISEASE INPOULTRY Joseph Bernard Schleicher, Lake Bluff, and William RodneyRoderick, Libertyville, Ill., assignors to Abbott Laboratories, Chicago,Ill. No Drawing. Continuation-impart of application Ser. No. 119,056,Feb. 25, 1971, now Patent No. 3,767,795. This application June 8, 1973,Ser. No. 366,933

Int. Cl. A61k 27/00 U.S. Cl. 424-212 4 Claims ABSTRACT OF THE DISCLOSUREA method of preventing or treating Mareks disease in poultry byadministering phosphonoacetic acid or its salts.

This application is a continuation-in-part of US. application Ser. No.119,056 filed Feb. 25, 1971, now U.S. Pat. 3,767,795 issued Oct. 23,1973.

Background of the Invention Mareks disease is caused by a herpes likevirus and is part of the avian leukosis complex. This group of diseasesis the greatest cause of economic loss in the US. poultry industry.Mareks disease is primarily a disease of younger chickens from two tofive months of age, although younger or older birds can be affected.Paralysis of both legs or wings is commonly observed due to tumors ofnerves leading to aflected parts. Other parts may be affected,particularly the visceral organs, the gonads or the eye. In the ocularform of the disease the iris becomes gray and is often distorted inshape. In severe cases, the bird becomes blind. The disease spreadsrapidly by contact from infected to un-infected birds, and young chicksare much more susceptible than older birds. Airborn infection is ofsignificance. Normal appearing birds may have mild lesions of thedisease and it is quite possible that such birds are carriers of theinfection. The infective agent occurs in blood cells, lymphoid tumorcells, plasma and feather follicles from affected birds. Day-old chicksinfected with a suspension of tumor cells from an infected bird showsigns of the disease in a few weeks. Many infected chicks will die bythe time they are eight weeks of age. There is no effective treatment ofthe disease nor any foolproof preventive measures that can be taken.Losses can generally be minimized by good hygiene and flock management.For example, isolating young stock from old hens during the rearingperiod to minimize exposure to the virus. Strains of chickens have beendeveloped that show genetic resistance to Mareks disease and somecontrol can be achieved by eliminating families that show a highincidence of the disease. A vaccine has also been shown to beeffecacious in reducing the paralysis associated with this disease.

Summary of the Invention The invention relates to a method of preventingor treating Mareks disease in poultry comprising administrating topoultry phosphonoacetic acid and its salts. The structure ofphosphonoacetic acid being as follows.

The compounds are administered either as the acid or as the alkali metalsalts particularly the mono, di, or trisodium salt or the calcium salt.

, 3,836,650 Patented Sept. 17, 1974 Detailed Description One-day-oldchicks were prophylactically treated with disodium phosphonoacetic acidor a dosage level'of 500 milligrams per kilogram per day, orally for 7days, at which time they were infected. intra-abdominally with Mareksvirus; half with 1500 units per bird and the other half with 6000 unitsper bird. The birds were then treated for an additional fourteen daysand observed daily for paralysis and death. The results are summarizedin the following tables.

Additionally, disodium phosphonoacetic acid is active against Mareksdisease virus in tissue culture at micrograms per milliliter ig/mi).

TABLE l.TOTAL NUMBER OFCHICKS PARALYZED Mareks Number of chicks disease,

virus Paralysis units/ Group bird Medication Initial Number Percent A1,500 Disodinm phosphono- 24 2 8 acetic acid. B 1,500 None 25 6 36 C6,000 Disodium phosphono 25 2 8 acetic acid.

D 6,000 None 25 9 36 E None do 29 0 0 TABLE 2.RATE OF PARALYSIS OFCHICKS Mareks disease,

Postvirus Paralysis infection units/ (No. of day Group bird Medicationchicks) 1,500 None 1 6,000 do 1 6,000 do 4 1,500 Disodliumphosphonoacetic 1 aci 1,500 None 2 6,000 do 1 1, 500 do 1 1, 500 do 16,000 .do 2 6,000 Disqgium phosphonoacetic 1 a0! 1,500 Diso aiumphosphonoacetic 1 am 6,000 None 1 1,500 o 1 6,000 Disqdliumphosphonoacetic 1 act It is apparent from the results that treatment ofchicks orally with 500 mg. per kg. per day of disodium phosphonoaceticacid for twenty-one days resulted in no toxicity. The incidence ofparalysis in non-treated chicks was found to be about four times asgreat as in treated birds, indicating that the compound had asignificant effect on the proliferation of Mareks virus. From Table 2 itis apparent that the first sign of paralysis in a treated bird occurredtwenty-seven days after infection whereas the first paralyzed bird inthe non-treated group occurred twenty-two days after infection,indicating that the compounds had a suppressive effect. on Mareks virus.

One day old chicks were prophylactically treated with disodiumphosphonoacetic acid at a dosage level of 500 mg. per kg. per day,orally for seven days at which time they were infected with Mareks virusJM strain at a dose of 2,000 plaque forming units per bird viaintraabdominal injection. The birds were then treated for an additional2, 5 or 8 weeks. The results are summarized in the following table.

'' TABLE 3.-THE EFFECT'OF DISODIUM PHosPHoNoACE'rIC ACID ON CHICKSINFECTED WITH THE IM STRAIN OF MAREKfS DISEASE VIRUS Birds saeiificedwhen severely paralyzed Survivors: Week Accumugross tumors latedfound at Group 0 1 2 3 4 5 6 7 8 9 totals A autopsy Normal control 0/272/27 0/27 0/27 0/27 0/27 0/27 0/27 0/27 0/27 0/25 0% 0/25 \grus control10/27 1/27 0/27 0/27 0/27 0/27 2/27 2/27 5/27 2/27 11/26 42% 0/15 rug convro 500 mg/kg/day, 3 weeks 0/11 0/11 0/11 0/11 0/11 0/11 0/11 0/11 0%0/11 500 mg/kg/day. 6 weeks. 1/11 2/11 0/11 0/11 0/11 0/11 0/11 5 3/1127% 0/8 1 V 500 nag/lrg/day, 9 Weeks 0/11 0/11 0/11 0/11 0/11 0/11 2/11b 2/11 18% 0/9 1rus an 'rugz. 500 mg/kg/day, 3 weeks 0/27 2/27 0/27 0/272/27 0/27 O/27 0/27 1/27 0/27 b 3/25 12% 0/22 500 mg/kg/day, 6 weeks--.0/27 2/27 0/27 0/27 1/27 4/27 2/27 0/27 0/27 0/27 b 7/25 28% 0/18 600mg/kg/day, 9 weeks 0/27 0/27 0/27 0/27 l/27 0/27 0/27 2/27 2/27 2/277/27 26% 1/20 A total of 7 chicks in this experiment died before theywere infected with the virus. These dead birds were not scored inAccumulated Totals.

Some degree of drug toxicity occurred in chicks th at were medicated for6 and 9 weeks.

NOTE

Normal control: No virus, no drug. Virus control Virus, no drug. Drugcontrol Drug only.

Medication: Disodium phosphonoacetic acid, 500 mg./kg./ day oral, for: 3weeks, 6 weeks, 9 weeks. Infection: Mareks virus, JM strain,intra-abdominal in ection, 2,000 p.f.u./bird.

From the table it can be seen that the (1) normal control chickensshowed no paralysis, although two birds died from unexplained reasons,(2) no toxicity was observed in chicks that were treated with disodiumphosphonoacetic acid at 500 mg. per kg. per day for three weeks.Medication for six weeks resulted in a mortality of 3/11 birds. Nineweeks of medication gave a mortality of 2/11 birds, and (3) the level ofparalysis was lower in the treated groups of chicks. There was, however,no dose response within the groups.

Administration of disodium phosphonoacetic acid at a dosage level of 100or 400 mg. per kg. per day for a period of nine weeks did not evidenceany efficacy in reduction of paralysis. Administration of the compoundfor at least three weeks at a dosage level of 500 mg. per kg. per day ispreferred. As is evident from the data, administration of the compoundto the birds prior to infection aides in preventing Mareks disease, withadministration for at least three weeks reducing the number of birdsafiected.

What is claimed is:

1. A method for treating Mareks virus infections in poultry which methodcomprises administering to poultry in need of said treatment aneffective amount for combating said Mareks virus infection ofphosphonoacetic acid or an alkali metal salt thereof.

2. A method as claimed in Claim 1 wherein the alkali metal salt isselected from the group consisting of the mono, di or trisodium salt.

3. A method as claimed in Claim 2 wherein the alkali metal salt isadministered orally at a dosage of about 500 mg./kg. daily. I

4. A method as claimed in Claim 3 wherein the alkali metal salt isadministered for a period of at least three weeks.

References Cited Stock et al., Cancer Research, vol. 20, No. 5, Part 2,pp. 193, 194 and 342 (June 1960).

Cancer Research, vol. 21, No. 8, Part 2, pp. 377, 378 and 451 (September1961).

Cancer Research, vol. 24, No. 2, Part 2, pp. 211, 212, 227 and 378(February 1964).

JEROME D. GOLDBERG, Primary Examiner

